Study of Ruxolitinib (INCB018424) Sustained Release Formulation in Myelofibrosis Patients

Browse trials for

• Primary Myelofibrosis 431
• Myeloproliferative Disorders 640

Keywords

• myelofibrosis
• myeloproliferative neoplasms
• PMF
• PET-MF
• PPV-MF

Primary Myelofibrosis

431 studies on the registry are indexed under Primary Myelofibrosis; 118 are open to participants now.

This study's enrollment of 41 is close to the median of 44 across 355 interventional studies indexed under Primary Myelofibrosis.

Lead sponsor

Incyte Corporation is the lead sponsor of 288 studies on the registry; 35 are open to participants now.

Of its 148 completed or terminated interventional studies of FDA-regulated products, 94 (64%) have results posted.

Study arms

• Experimental
  Ruxolitinib 25 mg SR/10, 15, or 20 mg IR

  Participants began administration with 25 mg ruxolitinib sustained release (SR) once daily (QD). After 8 weeks, if there was inadequate efficacy, the dose level could be titrated to 50 mg SR QD or 25 mg SR every other day (QOD) alternating with 50 mg SR QOD. At Week 16, participants transitioned to ruxolitinib 10, 15, or 20 mg immediate release (IR) orally twice daily. Participants who continued to demonstrate benefit in the opinion of the investigator could remain on ruxolitinib IR until the last participant completed Week 36 or the commercial availability of ruxolitinib IR, whichever was earlier; the dose received was based on platelet counts at the time of transition.

  Drug: Ruxolitinib

Interventions

• DrugRuxolitinib

  Ruxolitinib was supplied as SR and IR formulated tablets.

  Also known as: INCB018424

Primary outcomes

1. Percentage of Participants With at Least 1 Adverse Event From Baseline Through Week 16

   Time frame: Baseline to Week 16

2. Overall Response (OR) at Week 16

   The investigator graded OR according to the International Working Group for Myelofibrosis Research and Therapy criteria for treatment response. As bone marrow biopsies were not taken after baseline, the best achievable response was clinical improvement which required 1 of the following in the absence of progressive disease (PD): (1) A ≥ 2 g/dL increase in hemoglobin level or (2) either a palpable ≥ 50% reduction of splenomegaly of a spleen ≥ 10 cm at baseline or a spleen palpable at \> 5 cm at baseline becoming not palpable. PD required 1 of the following: (1) Progressive splenomegaly defined by the appearance of previously absent splenomegaly that was palpable at \> 5 cm below the left costal margin or a ≥ 100% increase in palpable distance for baseline splenomegaly of 5-10 cm or a ≥ 50% increase in palpable distance for baseline splenomegaly of \> 10 cm or (2) an increase in peripheral blood blast percentage to ≥ 20% that lasted for ≥ 8 weeks. Stable disease: None of the above.

   Time frame: Baseline to Week 16

Secondary outcomes

1. Change From Baseline in Spleen Volume at Week 16

   Spleen volume was measured by magnetic resonance imaging (or by computed tomography \[CT\] in applicable participants). Scans were read by a central reader. Spleen volume was obtained by outlining the circumference of the organ and determining the volume using the validated technique of least squares.

   Time frame: Baseline to Week 16

2. Change From Baseline in Spleen Length at Week 16

   Spleen length was measured in centimeters by palpation.

   Time frame: Baseline to Week 16

3. Percentage of Participants With ≥ 35% Reduction in Spleen Volume at Week 16 From Baseline

   Spleen volume was measured by magnetic resonance imaging (or by computed tomography \[CT\] in applicable participants). Scans were read by a central reader. Spleen volume was obtained by outlining the circumference of the organ and determining the volume using the validated technique of least squares.

   Time frame: Baseline to Week 16

4. Change From Baseline in the Total Symptom Score at Week 16

   Symptoms of myelofibrosis were assessed using the modified Myelofibrosis Symptom Assessment Form v2.0 diary that was to be completed by participants each night. The 7 symptoms (night sweats, itchiness, abdominal pain, pain under the ribs on left side, feeling of fullness \[early satiety\], bone/muscle pain, inactivity) were each rated on a scale from 0 (absent) to 10 (worst imaginable). The total symptom score was the sum of 6 of the 7 symptoms (inactivity was not included) and ranged from 0 to 60. A lower score indicated fewer symptoms. A negative change score indicated improvement.

   Time frame: Baseline to Week 16

5. Percentage of Participants With a ≥ 50% Reduction From Baseline in the Total Symptom Score at Week 16

   Symptoms of myelofibrosis were assessed using the modified Myelofibrosis Symptom Assessment Form v2.0 diary that was to be completed by participants each night. The 7 symptoms (night sweats, itchiness, abdominal pain, pain under the ribs on left side, feeling of fullness \[early satiety\], bone/muscle pain, inactivity) were each rated on a scale from 0 (absent) to 10 (worst imaginable). The total symptom score was the sum of 6 of the 7 symptoms (inactivity was not included) and ranged from 0 to 60. A lower score indicated fewer symptoms.

   Time frame: Baseline to Week 16

6. Maximum Observed Plasma Concentration (Cmax) of Ruxolitinib 25 mg SR on Day 1

   Blood samples were collected prior to and at 0.5, 1, 2, 3, 4, 6, and 9 hours after administration of ruxolitinib 25 mg SR on Day 1 of the study. The concentration of ruxolitinib was determined in plasma samples by a validated LC/MS/MS assay. Standard non-compartmental pharmacokinetic methods were used to analyze the ruxolitinib plasma concentration data using WinNonlin® version 6.0.0 (Pharsight Corporation, Mountain View, CA). Cmax was taken directly from the observed plasma concentration data.

   Time frame: Day 1

7. Time to Reach the Maximum Plasma Concentration (Tmax) of Ruxolitinib 25 mg SR on Day 1

   Blood samples were collected prior to and at 0.5, 1, 2, 3, 4, 6, and 9 hours after administration of ruxolitinib 25 mg SR on Day 1 of the study. The concentration of ruxolitinib was determined in plasma samples by a validated LC/MS/MS assay. Standard noncompartmental pharmacokinetic methods were used to analyze the ruxolitinib plasma concentration data using WinNonlin® version 6.0.0 (Pharsight Corporation, Mountain View, CA). Tmax was taken directly from the observed plasma concentration data.

   Time frame: Day 1

8. Area Under the Plasma Concentration-time Curve (AUC) of Ruxolitinib 25 mg SR on Day 1

   Blood samples were collected prior to and at 0.5, 1, 2, 3, 4, 6, and 9 hours after administration of ruxolitinib 25 mg SR on Day 1 of the study. The concentration of ruxolitinib was determined in plasma samples by a validated LC/MS/MS assay. The area under the plasma concentration-time curve (AUC) was derived from the plasma concentrations using a non-compartmental method and computed using the linear trapezoidal rule for increasing concentrations and the log-trapezoidal rule for decreasing concentrations with the software WinNonlin® version 6.0.0 (Pharsight Corporation, Mountain View, CA).

   Time frame: Day 1

Baseline characteristics